Methodological approach for an integrated female-specific study of anxiety and smoking comorbidity.

Two primary ovarian hormones that fluctuate across the female menstrual cycle-estradiol and progesterone-have been independently linked in separate literatures to nicotine reinforcement and anxiety psychopathology. We identify existing methodological limitations in these literatures, describe an example protocol that was developed to address such limitations, highlight case examples, and offer insights on the resulting advantages and challenges. This protocol was an observational, prospective, within-subjects study of female cigarette smokers who were followed over the course of a complete menstrual cycle.

Validation of a monoclonal unconjugated estriol antibody for use in prenatal maternal serum screening.

Objectives: Unconjugated estriol (uE3) is used as a marker for fetal aneuploidy in maternal serum screening tests. The goal of this study was to examine the validity of a new immunoassay for uE3 that uses a monoclonal antibody (m-uE3) rather than the more commonly used polyclonal antibody (p-uE3).

Setting: Assays were performed in the Special Chemistry laboratory at Women and Infants Hospital of Rhode Island.

Surveillance of SARS-CoV-2 Antibodies in Early 2020 among Rhode Island Pregnancies.

Objective: Limited data are available on the performance of SARS-CoV-2 antibody assays and data collected during pregnancy vary widely. The objective of this study was to estimate the seroprevalence of antibodies against SARS-CoV-2 in pregnant individuals in Rhode Island and to evaluate whether the prevalence differed by month of collection, age, county of residence, or economic status as estimated by zip code.

Methods: Pre-pandemic (2019) and early pandemic (2020) serum samples, collected for prenatal screening between 15 and 22 weeks of gestation, were analyzed utilizing two SARS-CoV-2 immunoglobulin G (IgG) automated assays that targeted the viral nucleocapsid (anti-N) or spike (anti-S) receptor binding domain proteins.

Assessment of a Simplified Cell-Free DNA Method for Prenatal Down Syndrome Screening.

Background: Prenatal screening for common trisomies via cell-free (cfDNA) is usually implemented by technologies utilizing massively parallel sequencing, stringent environmental controls, complex bioinformatics, and molecular expertise. An alternative and less complex methodology utilizes rolling circle amplification (RCA). Further evaluation of its performance and related requirements are warranted.

Association between a history of depression and anti-müllerian hormone among late-reproductive aged women: the Harvard study of moods and cycles.

Background: There is conflicting evidence regarding the association between a history of depression and risk of early menopause. In a cohort of premenopausal women, we investigated the association between depression history and ovarian reserve, as measured by anti-müllerian hormone (AMH).

Methods: The Harvard Study of Moods and Cycles (HSMC) was a prospective cohort study of women living in the Boston, MA metropolitan-area (1995-1999).

Serum Decorin, Biglycan, and Extracellular Matrix Component Expression in Preterm Birth.

Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue matrix and tensile strength of human fetal membranes and have been previously linked to PPROM. Extracellular matrix proteins, such as matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), TIMP metallopeptidase inhibitor 1 (TIMP-1), TIMP metallopeptidase inhibitor 2 (TIMP-2), and collagen VI (COL-6), have also been linked to PPROM and may have utility in a serum-based screening model for this condition.

Adjusting antimüllerian hormone levels for age and body mass index improves detection of polycystic ovary syndrome.

Objective: To examine whether accounting for a woman's age and body mass index (BMI) would improve the ability of antimüllerian hormone (AMH) to distinguish between women with (cases) and without (controls) polycystic ovarian syndrome (PCOS).

Design: An opportunistic case-control dataset of reproductive age women having evaluations for PCOS as defined by National Institutes of Health criteria.

Setting: Two medical centers in the United States enrolled women.

Antimüllerian Hormone Levels Are Not Altered by Glucose Challenge or a Meal.

Background: Measurement of antimüllerian hormone (AMH) is used to assess ovarian reserve. Circulating levels of AMH correlate with antral follicle count, with relatively high levels indicating an ample reserve of primary and preantral follicles in the ovary. AMH levels are stable with dilution and freezer storage, and are not altered by hemolysis or menstrual cycle day in young women of reproductive age.

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS.

Purpose: The pro-inflammatory advanced glycation end products (AGEs) and their anti-inflammatory soluble receptors, sRAGE, play a role in the pathogenesis of PCOS. There is a correlation between vitamin D (vit D) and sRAGE in the serum, whereby vit D replacement increases serum sRAGE levels in women with PCOS, thus incurring a protective anti-inflammatory role.

Objective: This study aims to compare levels of sRAGE, N-carboxymethyl-lysine (CML; one of the AGEs), and 25-hydroxy-vit D in the follicular fluid (FF) of women with or without PCOS, and to evaluate the correlation between sRAGE and 25-hydroxy-vit D in the FF.

Measuring maternal serum screening markers for Down's syndrome in plasma collected for cell-free DNA testing.

Objectives To determine whether maternal plasma collected in cell-free DNA stabilizing tubes is suitable for measuring prenatal screening 'serum' markers. Methods Matched plasma and serum samples were collected from 41 second trimester and 42 first trimester non-Down's syndrome pregnancies. Second trimester samples were tested for alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A (Beckman Coulter DxI immunoassay).

The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population.

Objective: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population.

Methods: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures.

Where have all the trisomies gone?

Providing reliable prenatal screening performance estimates is critical for patient counseling and policy-making. Women who choose prenatal screening for aneuploidy are likely to be concerned not only with the common aneuploidies but with all causes of intellectual disability and serious birth defects. Sequential prenatal screening (combined serum and ultrasound testing) for aneuploidy detection commonly is offered as a primary screening test.

Cut-off levels for hyperandrogenemia among Samoan women: An improved methodology for deriving normative data in an obese population.

Objective: To define biochemical hyperandrogenemia (HA) among a population-based sample of reproductive-aged Samoan women, taking into consideration their high BMI levels.

Design And Methods: A secondary analysis was performed among a cross-sectional sample of Samoan women aged 25-39years (n=494) who were part of a larger genome-wide association study (GWAS) of adiposity. Women indicating pregnancy/lactation, hysterectomy, oophorectomy, cancer treatment, or use of contraceptive injections were excluded from the study.

Evaluating first trimester maternal serum screening combinations for Down syndrome suitable for use with reflexive secondary screening via sequencing of cell free DNA: high detection with low rates of invasive procedures.

Objectives: Examine primary Down syndrome screening using combinations of first trimester serum markers, with and without sequencing of cell free DNA as a secondary reflexive test.

Methods: Samples from 40 Down syndrome cases were matched with five control samples and tested for PAPP-A, free β, AFP, inhibin-A and PlGF. Results were converted to weight-adjusted multiples of the median (MoM) and population parameters computed.

The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies.

Maternal plasma contains circulating cell-free DNA fragments originating from both the mother and the placenta. The proportion derived from the placenta is known as the fetal fraction. When measured between 10 and 20 gestational weeks, the average fetal fraction in the maternal plasma is 10% to 15% but can range from under 3% to over 30%.

Feasibility of using plasma rather than serum in first and second trimester multiple marker Down's syndrome screening.

Objective: To compare maternal plasma with serum for measuring markers currently used in first and second trimester screening for Down's syndrome.

Setting: A laboratory-based investigation of two sample types in assays used in prenatal screening for Down's syndrome.

Methods: A paired data-set included both plasma and serum from 101 pregnant women.

DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations.

Objective: Studies on prenatal testing for Down syndrome (trisomy 21), trisomy 18, and trisomy 13 by massively parallel shotgun sequencing (MPSS) of circulating cell free DNA have been, for the most part, limited to singleton pregnancies. If MPSS testing is offered clinically, it is important to know if these trisomies will also be identified in multiple pregnancies.

Method: Among a cohort of 4664 high-risk pregnancies, maternal plasma samples were tested from 25 twin pregnancies (17 euploid, five discordant and two concordant for Down syndrome; one discordant for trisomy 13) and two euploid triplet pregnancies [Correction made here after initial online publication.

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.

Purpose: To determine whether maternal plasma cell-free DNA sequencing can effectively identify trisomy 18 and 13.

Methods: Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.

DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.

Purpose: Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.

Methods: A blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome.

Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders.

Lower levels of LINE-1 methylation in peripheral blood have been previously associated with risk of developing non-communicable conditions, the most well-explored of these being cancer, although recent research has begun to link altered LINE-1 methylation and cardiovascular disease. We examined the relationship between LINE-1 methylation and factors associated with metabolic and cardiovascular diseases through quantitative bisulfite pyrosequencing in DNA from peripheral blood samples from participants of the Samoan Family Study of Overweight and Diabetes (2002-03). The sample included 355 adult Samoans (88 men and 267 women) from both American Samoa and Samoa.

The relationship between tumor MSLN methylation and serum mesothelin (SMRP) in mesothelioma.

Malignant pleural mesothelioma (MPM) remains a cancer of poor prognosis. It is hoped that implementation of effective screening biomarkers will lead to earlier diagnoses and improved outcomes. Serum-measured soluble mesothelin-related peptide (SMRP) has been demonstrated to have excellent specificity for MPM, but poor sensitivity precludes its use as a screening biomarker.

Early onset preeclampsia and second trimester serum markers.

Objective: To examine serum markers measured in the second trimester to identify women who subsequently develop preeclampsia.

Methods: Clinically defined preeclampsia was confirmed in 45 women who had provided a serum sample as part of Down syndrome screening. Preeclampsia was categorized as mild or severe, as well as early (<32 weeks) or late onset.